Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia.

Low-grade inflammation has been associated with negative symptoms in patients with schizophrenia. Of these symptoms, deficits in motivation and pleasure, especially in the domain of avolition, are particularly disabling. Effects of inflammation on motivational deficits in patients with depression are associated with disruptions in corticostriatal reward circuitry involving the inferior ventral striatum (iVS) and ventromedial prefrontal cortex (vmPFC). Accordingly, we examined the relationships among inflammation, negative symptoms, and corticostriatal reward circuitry in patients with schizophrenia. Negative symptoms and high sensitivity C-reactive protein (hsCRP) were obtained in 57 individuals with schizophrenia. Resting state functional connectivity (rsFC) was obtained from a subset of 43 of these individuals. Associations were tested between hsCRP and the motivation and pleasure (MAP) and expressivity (EXP) dimensions of the Brief Negative Symptom Scale (BNSS) as well as targeted rsFC between iVS and vmPFC. Covariates in all statistical models included age, sex, race, smoking, body mass index, depression, and chlorpromazine equivalents. hsCRP was significantly associated with BNSS MAP (β = 0.34, p_corr = 0.022, specifically the domains of avolition and asociality (p < 0.05), but not BNSS EXP (β = -0.17, p_corr = 0.57) or the domains of blunted affect or alogia (both p > 0.05). hsCRP was also significantly associated with decreased rsFC from right iVS to vmPFC (β=-0.37, p_corr = 0.029), which in turn, was associated with increased avolition in individuals with higher (hsCRP >2 mg/L) but not lower inflammation (β=-14.01, p = 0.007 vs. β = 0.07, p = 0.77, respectively). hsCRP was associated with reduced avolition and corticostriatal rsFC in patients with schizophrenia and increased inflammation, underscoring the need for further research to replicate these associations with brain connectivity changes in this subgroup of individuals with schizophrenia.